{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T08:18:06Z","timestamp":1777364286310,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,6,22]],"date-time":"2015-06-22T00:00:00Z","timestamp":1434931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Patients with decompensated cirrhosis are susceptible to infection. Innate immune dysfunction and development of organ failure are considered to underlie this. A rodent model of liver disease sharing these phenotypic features would assist <jats:italic>in\u00a0vivo<\/jats:italic> study of underlying mechanisms and testing of therapeutics. We evaluated three models to identify which demonstrated the greatest clinical and immunological phenotypic similarity to patients with acutely decompensated (<jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>) cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We selected Bile Duct Ligation (<jats:styled-content style=\"fixed-case\">BDL<\/jats:styled-content>) rats at 4\u00a0weeks, <jats:styled-content style=\"fixed-case\">BDL<\/jats:styled-content> mice at 14\u00a0days and Carbon tetrachloride (<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>) mice at 10\u00a0weeks (with studies performed 7\u00a0days after final <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> infection). We examined organ dysfunction, inflammatory response to carrageenan\u2010in\u2010paw, plasma eicosanoid concentrations, macrophage cytokine production and responses to peritoneal infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bile duct ligation caused sarcopenia, liver, cardiovascular and renal dysfunction whereas <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> mice demonstrated no clinical abnormalities. <jats:styled-content style=\"fixed-case\">BDL<\/jats:styled-content> rodents exhibited depressed response to carrageenan\u2010in\u2010paw unlike <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> mice. <jats:styled-content style=\"fixed-case\">BDL<\/jats:styled-content> rats have slightly elevated plasma eicosanoid levels and plasma showed partial <jats:styled-content style=\"fixed-case\">PGE<\/jats:styled-content><jats:sub>2<\/jats:sub>\u2010mediated immune suppression whereas <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> mice did not. Plasma <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>x was elevated in patients with acute or chronic liver failure (Ao<jats:styled-content style=\"fixed-case\">CLF<\/jats:styled-content>) compared to healthy volunteers and <jats:styled-content style=\"fixed-case\">BDL<\/jats:styled-content> rodents but not <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> mice. Elevated nitric oxide (<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>) via inducible nitric oxide synthase (<jats:styled-content style=\"fixed-case\">iNOS<\/jats:styled-content>) mediates defective leucocyte trafficking in <jats:styled-content style=\"fixed-case\">BDL<\/jats:styled-content> rodent models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We conclude that <jats:styled-content style=\"fixed-case\">BDL<\/jats:styled-content> mice and rats are not simply models of cholestatic liver injury but may be used to study mechanisms underlying poor outcome from infection in <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> and have identified elevated <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> as a potential mediator of depressed leucocyte trafficking.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12876","type":"journal-article","created":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T14:17:58Z","timestamp":1432736278000},"page":"837-846","source":"Crossref","is-referenced-by-count":22,"title":["Bile duct\u2010ligated mice exhibit multiple phenotypic similarities to acute\u00a0decompensation patients despite histological differences"],"prefix":"10.1111","volume":"36","author":[{"given":"Alastair","family":"O'Brien","sequence":"first","affiliation":[{"name":"Centre for Clinical Pharmacology and Therapeutics Division of Medicine University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"China","sequence":"additional","affiliation":[{"name":"Centre for Clinical Pharmacology and Therapeutics Division of Medicine University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen A.","family":"Massey","sequence":"additional","affiliation":[{"name":"Manchester Pharmacy School Faculty of Medical and Human Sciences the University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Nicolaou","sequence":"additional","affiliation":[{"name":"Manchester Pharmacy School Faculty of Medical and Human Sciences the University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison","family":"Winstanley","sequence":"additional","affiliation":[{"name":"Department of Histopathology University College London Hospitals London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justine","family":"Newson","sequence":"additional","affiliation":[{"name":"Centre for Clinical Pharmacology and Therapeutics Division of Medicine University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Hobbs","sequence":"additional","affiliation":[{"name":"St. Bart's &amp; the London Medical School London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsiana","family":"Audzevich","sequence":"additional","affiliation":[{"name":"Centre for Clinical Pharmacology and Therapeutics Division of Medicine University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek W.","family":"Gilroy","sequence":"additional","affiliation":[{"name":"Manchester Pharmacy School Faculty of Medical and Human Sciences the University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.12.005"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000317248"},{"key":"e_1_2_8_4_1","first-page":"616","article-title":"Bacterial infections in liver cirrhosis","volume":"31","author":"Navasa M","year":"1999","journal-title":"Ital J Gastroenterol Hepatol"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.282.6272.1262"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109391"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840060217"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.30082"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-012-2523-2"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27077"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3516"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0310149"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i23.7252"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00041.2014"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21599"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.11.034"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.3331"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.2697"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e31820860f5"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20130642"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2014.09.004"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.28702"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-1536-6-19"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.09.008"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-009-0990-2"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1086\/315742"},{"key":"e_1_2_8_27_1","unstructured":"BrownS.PHE launches local authority liver disease profiles. 2014 Available at:https:\/\/www.gov.uk\/government\/news\/phe-launches-local-authority-liver-disease-profiles. 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